JP5405736B2 - Dialysis aqueous solution - Google Patents

Description

  The present invention relates to an aqueous solution for dialysis using neutral electrolyzed water obtained by electrolyzing physiological saline with an electrolyzer equipped with a low-frequency vibration stirrer.

  It is known that when water is electrolyzed using a device having a diaphragm, hydrogen and oxygen are generated in the electrode portion. In this case, ion migration due to electrical attraction occurs in the aqueous solution. As a result, an acidic substance is generated on the anode side across the diaphragm, and the solution becomes an acidic solution. On the other hand, an alkaline solution (reducing solution) is formed on the cathode side. Therefore, when water is electrolyzed in a two-tank electrolytic tank or a three-tank electrolytic tank using an electrolyte diaphragm, an acidic aqueous solution is produced on the anode side and an alkaline solution (reducing solution) is produced on the cathode side. Is done.

These electrolytic solutions have performances as pH adjusting agents, oxidizing agents, and reducing agents, and have been used as functional water in a wide range of fields such as medical, electronic industry, agriculture, and food industry.
By the way, the electrolytic solution is strongly acidic water or strong alkaline water, and the pH of the strong acid water is 2.7 or less, and the pH of the strong electrolyte water is 11 or more. Accordingly, since bacteria, microorganisms and the like cannot survive in these pH ranges, the medical field has applicability only in a limited range such as disinfection of medical equipment.

  Therefore, in order to be able to use the electrolyzed water widely in the medical field including the human body, it is neutral electrolyzed water, and it is required to ensure safety. Neutral electrolyzed water having various functions is obtained by mixing and neutralizing both strongly acidic water and strong alkaline water obtained as described above, and only using it as neutral electrolyzed water. The current situation is that it was not obtained by direct electrolysis.

Neutral electrolyzed water described in Patent Document 1 is an example of neutral electrolyzed water that may serve this purpose. This neutral electrolyzed water is neutral electrolyzed water obtained by electrolyzing water containing salt with an electrolytic tank equipped with a low-frequency vibration stirrer, and has various functions. It is superior to any electrolyzed water such as acidic electrolyzed water or alkaline electrolyzed water, and is used as an aqueous solution for sterilization, health drinks, food washing, medical use, cosmetics, various toiletries, etc. Has been.
International Publication WO2006 / 041001 A1 Publication

The present inventors have paid attention to various functions of the neutral electrolyzed water and have studied various applications thereof. Among them, when physiological saline was used as an aqueous solution to be subjected to this electrolysis, the neutral electrolyzed water obtained thereby retained various functions possessed by the conventional neutral electrolyzed water. As a result, it was confirmed that safety was ensured as an aqueous solution that is physiologically used for medical purposes by exhibiting an extremely strong bactericidal action and further using physiological saline.
In addition, it has been newly found that this neutral electrolyzed water is extremely effective when used as an aqueous solution for dialysis.

That is, neutral electrolyzed water obtained by electrolyzing physiological saline has a very strong bactericidal action, and since it is an aqueous solution in a neutral region, when applied as a solution for dialysis preparations, It has been found that the solution is extremely effective for dialysis.
Furthermore, the neutral electrolyzed water or the physiological saline obtained by mixing with another physiological saline is used as a disinfectant for catheters or catheter joints in peritoneal dialysis, or in the body cavity, the boundary between the subcutaneous and skin, and the skin. It has been found that it is extremely effective as a disinfectant for the treatment of peritonitis in peritoneal dialysis.

Currently, there are about 270,000 patients with end-stage renal failure in Japan, and these patients receive dialysis therapy almost daily, on a daily basis or continuously, but extracorporeal circulation is required for dialysis. Therefore, there is a risk of infection and is constantly back to back. In fact, according to a survey by the Japanese Society for Dialysis Medicine, such infectious diseases account for 19.9% of the causes of death and are ranked second in the cause of death.
Therefore, if a dialysate without risk of infection is obtained, dialysis therapy that avoids the negative factor of infection becomes possible, and the enlightenment given to these patients becomes enormous.
The inventors of the present invention have newly found that neutral electrolyzed water obtained by electrolyzing physiological saline with an electrolytic tank equipped with a low-frequency vibration stirrer solves these points, and has completed the present invention. I came to let you.

Accordingly, an object of the present invention is to provide an aqueous solution for dialysis that has no risk of infection.
More specifically, it is used for dialysis solution as hemodialysis therapy or dialysis solution as peritoneal dialysis therapy without risk for infection, or for cleaning dialysate related circuits. It is an object of the present invention to provide an aqueous solution for dialysis, and further, a disinfectant for catheters or catheter joints in peritoneal dialysis, or a disinfectant for body cavity, the boundary between subcutaneous and skin, and skin.

The present invention based on the basic mode for solving such a problem is based on direct current or pulse current while vibrating physiological saline with a period of 10 to 200 Hz and an amplitude vibration of 0.01 to 15 mm. An aqueous solution for dialysis comprising neutral electrolyzed water containing 1 to 500 ppm of residual chlorine obtained by electrolysis at a voltage of ˜30 V and a current density of 5 to 300 A / dm ² .

  In particular, the present invention is the above-mentioned aqueous solution for dialysis characterized by being used as a dialysis solution as hemodialysis therapy or a dialysis solution as peritoneal dialysis therapy.

  More specifically, the present invention is the above-mentioned aqueous solution for dialysis, which is used as a dialysis solution for dissolving an electrolyte component, glucose and amino acids.

  In particular, the present invention is the above aqueous solution for dialysis characterized by using only sodium hydrogen carbonate as an alkalizing agent.

  Furthermore, as another aspect, the present invention is the above-described aqueous solution for dialysis, which is used for cleaning a dialysate-related circuit.

  Further, the present invention provides the above-mentioned dialysis, which is used as a disinfectant for a peritoneal catheter or a catheter joint in peritoneal dialysis, or as a disinfectant for a body cavity, a boundary between skin and skin and a skin disinfectant in peritoneal dialysis. This disinfecting solution is an aqueous solution for dialysis that may be used by mixing with another physiological saline.

  In the present invention, unlike conventional electrolyzed water, an aqueous solution for dialysis using neutral electrolyzed water obtained by electrolyzing physiological saline with an electrolyzer equipped with a specific low-frequency vibration stirrer. One of the characteristics is that the excellent sterilizing action results in an extremely excellent dialysis aqueous solution.

Therefore, the present invention specifically exhibits the following effects.
1. Since the aqueous dialysis solution provided by the present invention exerts an extremely strong bactericidal action, it can be used to clean the dialysate-related circuit before the start of dialysis therapy. There is an advantage that it is possible to dispel the fear of influx of bacterial toxins into the living body.
2. Since the aqueous solution for dialysis provided by the present invention is obtained by electrolyzing physiological saline, the residual chlorine decreases stepwise, and an extremely powerful bactericidal effect immediately before the start of dialysis therapy. Therefore, this aqueous solution for dialysis can be used as a dialysis solution as it is as an electrolyte component such as sodium, potassium, calcium, magnesium, chlorine, bicarbonate, glucose, and so on. It can be used as a dialysis solution used as a solution for nutrients such as sugars and amino acids.
3. The aqueous solution for dialysis of the present invention, when used as an electrolyte for dialysate, alkalizing agent, glucose solution, dissolves electrolyte components such as sodium chloride, potassium chloride, calcium chloride, magnesium chloride first, Sodium bicarbonate is then dissolved, but even in this case, these electrolyte components can be dissolved without forming insoluble bicarbonate, and at this point the pH of the solution is moderate. It has the advantage that it does not require the addition of an acid as a pH regulator.
4). In any case where the aqueous dialysis solution of the present invention is used for cleaning a dialysate-related circuit, or used as a solution as a dialysate, acid addition is not required. There is no risk of corrosion.
5. Even when used as a lysis solution for dialysis, since physiological saline is used, it has excellent biocompatibility and high safety, and has the advantage of not damaging the QOL of hemodialysis patients. Yes.
6). In addition, as a disinfectant for peritoneal catheters or catheter joints in peritoneal dialysis, or as a disinfectant for intraperitoneal, subcutaneous and skin boundaries and skin in peritoneal dialysis, The onset can be suppressed, and it gives a great deal of light to the patient.

The aqueous solution for dialysis provided by the present invention basically comprises neutral electrolyzed water obtained by electrolyzing physiological saline with an electrolytic cell equipped with a low-frequency vibration stirrer.
Such neutral electrolyzed water is specifically obtained by the method and apparatus described in Patent Document 1, and more specifically, as described above, 10 to 200 Hz so as to flow physiological saline. Residual chlorine of 1 to 500 ppm obtained by electrolysis with a voltage of 1 to 30 V and a current density of 5 to 300 A / dm ² by direct current or pulse current while vibrating with a period and an amplitude vibration of 0.01 to 15 mm It is the aqueous solution for dialysis which consists of neutral electrolyzed water containing.
This aqueous solution for dialysis is characterized in that no residual chlorine concentration is observed in the atmosphere.
In other words, ionized chlorine (volatile chlorine gas) is confined in a lump of water molecules, so that this dialysis aqueous solution does not have a chlorine odor for its concentration, and the residual chlorine life is as long as 3 years. It is assumed that there is.

  In the present invention, the dialysis aqueous solution refers to an aqueous solution used for dialysis itself, a disinfectant for a peritoneal catheter or a catheter coupling part in peritoneal dialysis, or a body cavity, a subcutaneous-skin boundary part and a skin in peritoneal dialysis therapy. An aqueous solution for dialysis as a disinfectant.

  Specific means for the preparation is described in detail in Patent Document 1, and the description in Patent Document 1 is incorporated in this specification as a part of this specification.

In Patent Document 1, specifically, treated water containing at least one salt selected from the group consisting of sodium chloride, potassium chloride, and calcium chloride and water is electrically supplied by an electrolytic cell equipped with a low-frequency vibration stirrer. Although the neutral electrolyzed water obtained by decomposition | disassembly is disclosed, the content density | concentration of the salt in that case is 0.05-10 weight%, and there is no idea of electrolyzing physiological saline.
In the present invention, physiological saline is adopted as the aqueous solution to be subjected to this electrolysis, and the physiological saline is generally a sodium chloride aqueous solution prepared so as to be isotonic with the osmotic pressure of animal cells. Say. In the case of mammals including humans, the salt concentration is about 0.8 to 0.9%.

In the neutral electrolyzed water of the present invention, neutral electrolyzed water containing 1 to 500 ppm of residual chlorine is prepared by performing electrolysis under the conditions described in Patent Document 1 described above.
Due to the presence of such residual chlorine, the neutral electrolyzed water exerts an extremely strong bactericidal action. However, in the dialysis aqueous solution of the present invention, if about 20 ppm of residual chlorine is contained, a substantially complete bactericidal effect is obtained. It can be demonstrated.
It has been found that even when the residual chlorine concentration is 1 to 5 ppm, the bactericidal effect is exhibited and the concentration is harmless to the human body.
In addition, about the neutral electrolyzed water containing a residual chlorine to 5 ppm, it is good to use the salt solution which contained sodium chloride concentration as a whole, and adjusted to 0.9% (9 g / L), ie, physiological saline.
In such a solution, neutral electrolyzed water can be appropriately mixed with another physiological saline.

The basis in today's medical solutions is a solution containing 0.9% sodium chloride, which is treated as the safest solution and is called saline. The physiological saline itself has no antibacterial and bactericidal action, and a liquid maintained aseptically is used. Therefore, the present condition is that a physiological saline containing an antibacterial agent or disinfectant is used for disinfection or disinfection.
However, the neutral electrolyzed water prepared above exhibits an extremely strong bactericidal action as it is (see the examples described later), and for such bactericidal action, it can be used to clean dialysis related circuits, As another application, it has been found that application as a disinfecting aqueous solution or a spray-type disinfecting solution is also possible.
Various other applications are also considered, and these are specifically described in Patent Document 1, but application as an aqueous solution for dialysis was first proposed by the present inventor.

Therefore, as described above, the aqueous solution for dialysis provided by the present invention can be used as a cleaning solution for aseptically purifying the dialysate-related circuit in the artificial kidney, as one aspect thereof.
Usually, distilled water, purified water, or reverse osmosis water is used as a dialysis solution as a basic solution, and a cleaning solution other than hot water is commercially available as a disinfecting solution. In this case, tap water or the like is used as hot water.

  The dialysis-related circuit to be purified by the dialysis aqueous solution of the present invention starts from the tap water inlet which is the origin of the dialysis solution, from the reservoir, reverse osmosis device to the dialysate circuit in the artificial kidney device, Refers to all parts from the dialyzer to the filter. Usually, hypochlorous acid, peracetic acid, citric acid, hot water (boiling water) and the like are used for sterilization and purification of these. Therefore, when organic acids such as hypochlorous acid, peracetic acid and citric acid are used, these solutions are usually discarded after neutralizing the acid with caustic soda water or the like. Therefore, a detoxification device such as a neutralizer addition device is required. These acids or alkalis are highly toxic by themselves, and there is a risk of adverse effects on living bodies. The aqueous solution for dialysis of the present invention has the advantage that there is no such danger.

  In addition, when purifying dialysis-related circuits, if the maximum residual concentration is raised to 500 ppm or higher, the bactericidal / antibacterial effect is further increased, but if it is accidentally contacted with a living body, the risk of life threatening increases. . However, after purifying for a certain period of time with neutral electrolyzed water containing high concentration residual chlorine, switching to neutral electrolyzed water containing low concentration residual chlorine can avoid this risk. It becomes possible.

  As described above, by using the neutral electrolyzed water of the present invention for sterilization / disinfection and cleaning of the dialysate-related circuit, the purpose of cleaning the dialysis-related circuit can be achieved.

  On the other hand, the neutral electrolyzed water prepared according to the present invention can be used as a dialysis solution itself used for hemodialysis or peritoneal dialysis therapy as another embodiment. Such dialysate is, for example, an aqueous solution in which sodium, potassium, calcium, magnesium, chlorine, sodium bicarbonate, glucose, amino acids, etc. are dissolved and contained in neutral electrolyzed water, and the pH near neutral is set as the pH. It has a dialysate.

  Specifically, the purpose is to maintain the electrolyte balance of a hemodialysis patient or peritoneal dialysis patient within a normal range, and as cations, sodium ions 80 to 200 mEq / L, potassium ions 0 to 6 mEq / L, calcium ions 0. A dialysis solution containing 5 to 5 mEq / L, magnesium ions 0.1 to 2.0 mEq / L; chlorine ions 80 to 200 mEq / L and bicarbonate ions 25 to 35 mEq / L as anions.

As the alkalizing agent, neutral electrolyzed water is used in the present invention, so that sodium hydrogen carbonate is used, and it is not necessary to use any other alkalizing agent.
As an electrolyte component constituting the above electrolyte balance, sodium chloride, calcium chloride, magnesium chloride or the like is preferably used.
Moreover, it is good to contain 50-200 mg / dL as glucose.
Furthermore, as amino acids, various amino acids including various essential amino acids are raised, and it is preferable to contain 1 to 7.5 w / v% as a total amino acid concentration.

  The dialysate usually contains acetic acid, glacial acetic acid, lactic acid, citric acid and the like in addition to sodium chloride, potassium chloride, magnesium chloride, sodium bicarbonate and glucose. An amino acid may or may not be added.

In hemodialysis, patients with acute and chronic renal failure who have lost their renal function are brought into contact with body fluid by contacting blood and dialysate through a semipermeable membrane, which is the main component of an artificial kidney called a dialyzer or filter. Is a means for excreting the waste product in the dialysis fluid, and further, dialysis performed to ensure the balance of various body fluid components.
The dialysate used for this purpose is indispensable for hemodialysis therapy. In general, in addition to electrolyte components such as sodium chloride, calcium chloride, magnesium chloride, etc., in order to maintain a pH close to that of body fluids. Further, lactate, acetate, carbonate and the like are contained as alkalizing agents. Glucose is also added to avoid hypoglycemia due to dialysis removal.

Peritoneal dialysis, on the other hand, causes patients with acute and chronic renal failure who have lost renal function to excrete waste products in body fluids into the dialysate by contacting blood and dialysate through a semipermeable membrane called the peritoneum. Further, dialysis is performed in order to ensure the balance of various body fluid components.
The dialysate for that purpose is indispensable for peritoneal dialysis therapy. In general, in addition to electrolyte components such as sodium chloride, calcium chloride, magnesium chloride, etc., it is alkalinized to maintain a pH close to that of body fluids. Lactates, acetates, carbonates and the like are contained as agents. Furthermore, glucose as an osmotic pressure substance for keeping the osmotic pressure higher than that of body fluid is also added in order to avoid water removal by ultrafiltration from the body.

In any of such hemodialysis and peritoneal dialysis, the dialysate needs to contain an alkalizing agent. At present, sodium hydrogen carbonate is the mainstream as this alkalizing agent, but the pH of the dialysate always shifts to the alkali side due to sodium hydrogen carbonate. In order to maintain this back to neutrality, organic acids such as acetic acid, lactic acid and citric acid are added. These organic acids also have the advantage of preventing the disadvantage that calcium chloride forms insoluble calcium carbonate.
On the other hand, in the case of organic acids contained in dialysate, for example, acetic acid is known to cause dialysis hypotension, dialysis difficulties, dialysis nutritional disorders, and the like. Citric acid is known to cause hypocalcemia and hemorrhage. Therefore, if such an essentially unnecessary acid is not contained, there is no side effect of the dialysate, and a stable dialysis therapy can be received for the patient.

In addition, almost all patients with chronic renal failure have metabolic acidosis. Although it is most physiological to use sodium bicarbonate for its correction, it is known to react with calcium chloride that needs to be included in the dialysate to produce an insoluble calcium carbonate precipitate. In reality, acetic acid, glacial acetic acid and citric acid are added. This is for increasing the solubility by allowing calcium to be present as a chelate, but is positioned as a material that should not be mixed.
In the case where the neutral electrified water of the present invention is used as a dialysate, sodium chloride and calcium chloride are formed without the formation of calcium carbonate precipitates without the addition of organic acids such as acetic acid, glacial acetic acid and citric acid. Thus, it is possible to prepare a dialysate containing an electrolyte component such as magnesium chloride, sodium hydrogen carbonate, and glucose.

  Addition of acetic acid, glacial acetic acid, citric acid, etc. to the dialysate is overcorrected by sodium bicarbonate added as an alkalizing agent, that is, to prevent alkalosis and to neutralize the dialysate, By using the neutral electrolyzed water of the present invention, it is possible to obtain a dialysate that uses only sodium bicarbonate as an alkalizing agent without adding these acids.

  In addition, in the dialysate used for hemodialysis or peritoneal dialysis, the pH of the solution is preferably about 7.0 to 7.5. In conventional dialysis fluids, sodium bicarbonate, sodium hydroxide, hydrochloric acid, acetic acid, glacial acetic acid, citric acid alone and mixtures thereof are generally used as pH regulators. The dialysate using electrolyzed electrolyzed water has the advantage that the pH can be maintained in the range of about 7.0 to 7.5 with only the most physiological sodium bicarbonate for the living body. Yes.

  As a method for preparing the dialysate of the present invention, for example, the following three specific methods can be used. That is, (1) dialysate composition sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium bicarbonate, glucose, and amino acids are powdered and dissolved in neutral electrolyzed water; (2) dialysate composition Certain sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose, and amino acids are dissolved and stored in neutral electrolyzed water. At the same time, sodium bicarbonate is dissolved separately in neutral electrolyzed water, and both are mixed immediately after dissolution; (3) Sodium chloride, potassium chloride, calcium chloride, and chloride constituting the dialysate composition and concentration in the reverse osmosis solution Magnesium is added, and the solution itself is electrolyzed in an electrolytic tank equipped with a low-frequency vibration stirrer, and subjected to neutral electrolytic water treatment. Glucose and amino acids are further dissolved in the resulting treatment solution. Next, as in (2) above, there are three methods, in which sodium hydrogen carbonate is separately dissolved in neutral electrolytic water and both are mixed immediately after dissolution.

In addition, selection of these methods can be selected according to the request | requirement of a patient, a medical staff, and the installation condition of a dialysis therapy implementation facility.
Needless to say, the dialysate preparation method is not limited to the above three methods, and there are various modifications.

  In the dialysate provided by the present invention, neutral electrolyzed water having a bactericidal action is used as a solution, but if the dialysate itself has bactericidal properties that do not harm the living body, Even after the actual hemodialysis therapy is started, accidental contamination by pathogenic microorganisms in the dialysate and filter of the dialysate can be prevented.

  Sterilization of dialysate can also be combined online by incorporating filtration methods using reverse osmosis membranes and sanitizing membranes that are routinely used for both central supply and personal dialysate. is there.

In addition, the peritoneal dialysis has a drawback of peritonitis due to infection with pathogenic microorganisms, particularly peritonitis in the catheter joint. Alternatively, it is possible to suppress the onset of peritonitis by using it as a body antiseptic solution in the body cavity, subcutaneous and skin, and skin disinfectant in peritoneal dialysis therapy.
In addition, when using as this disinfectant, another physiological saline can be appropriately mixed and diluted before use.
Therefore, the present invention also provides a disinfecting solution comprising such neutral physiological saline as another aspect.

Originally, the pH of the living body is maintained neutral, and the osmotic pressure is maintained at 270 to 280 mOsm / L. Conventionally, such antibacterial agents for living bodies have a pH biased toward acidity or alkalinity and an osmotic pressure biased toward the low osmotic pressure side or the high osmotic pressure side, and are only clinically applied only for external use such as the skin itself. Accordingly, in the current situation, disinfection / sterilization of blood vessels, body cavities, and the boundary between the subcutaneous and skin must rely on antibiotics.
The current state of reliance on antibiotics has resulted in a bacterial turnover phenomenon and has become a hotbed for nosocomial infections with the emergence of vancomycin-resistant strains and methicillin-resistant Staphylococcus aureus. Since the disinfecting solution provided by the present invention is a neutral physiological saline solution having antibacterial properties, it has an advantage that it can be applied to any part of a living body.

  EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to these examples.

Example 1: Sterilization effect of dialysis aqueous solution for cleaning dialysis related circuit using neutral electrolyzed water [test method]
Escherichia coli (E. coli: JCM 1649), Salmonella (S. enterica: JCM 1652), Pseudomonas aeruginosa (P. aeruginosa: JCM 5516) and Staphylococcus aureus (S. aureus) grown and cultured in tryptic sauce soy broth medium : JCM 2413), each cell was washed by centrifugation using sterile distilled water, and then resuspended in sterile distilled water to prepare a bacterial suspension.
For each bacterial cell, 0.4 mL of the bacterial suspension prepared above is described as 39.6 mL of sterilized distilled water and neutral electrolyzed water (hereinafter referred to as “α Torino-ST water”) as the dialysate of the present invention. The residual chlorine concentration of 5 ppm) was added to 39.6 mL and stirred. The number of viable bacteria in sterile distilled water is serially diluted using sterile phosphate buffered saline, and the number of viable bacteria in α-Torino-ST water is treated for a certain period of time and then immediately diluted as a processing stock solution without dilution. It measured by the plate dilution method (35 degreeC, 48 hours, aerobic culture) using the tripty sauce soy agar medium.

[result]
The results are summarized in Table 1 below.
As is clear from the results shown in the table, when α-trino-ST water was used, the number of viable bacteria decreased to 30 cells / mL or less, that is, to the measurement sensitivity or less.
Moreover, although it described as "Note 1" in the remarks column, colony formation was not able to be confirmed in the measurement (1 series) using 1 mL of this liquid.

Example 2: Electrolyte component / glucose solubility test 1 L of α-trino-ST water (residual chlorine concentration: 3 ppm), 6.25 g of sodium chloride, 0.18 g of potassium chloride, 0.37 g of calcium chloride dihydrate, chloride After adding 0.34 g of magnesium hexahydrate and 200 g of glucose and confirming dissolution, 2.52 g of sodium bicarbonate was further added and dissolved, and then the presence or absence of the formation of floating reaction products was visually observed.
The same components were dissolved in 1 L of ion-exchanged water as the target liquid, and after dissolution, the presence or absence of the formation of floating reactants and precipitates was visually observed.
Moreover, ion-exchanged water that does not dissolve anything was prepared.
As a result, as shown in Table 2 below, in the solution in which each component was dissolved in α-trino-ST water, formation of floating reaction products and precipitates was not observed. The formation of reactive floats and precipitates was observed.
In addition, no change was observed in the ion-exchanged water in which nothing was dissolved.

Example 3: Electrolyte component / glucose-containing dialysate pH and osmotic pressure test α-Torino-ST water (residual chlorine concentration: 4 solutions of 3 ppm, 5 ppm, 7 ppm and 10 ppm), 1 L, 6.25 g of sodium chloride, potassium chloride A dialysate was prepared by dissolving 0.18 g, calcium chloride dihydrate 0.37 g, magnesium chloride hexahydrate 0.34 g, glucose 1.26 g, and sodium bicarbonate 2.52 g.
On the other hand, the same dialysate components were dissolved in distilled water as a control dialysate.
The pH and osmotic pressure of each test solution were measured with a pH meter manufactured by Horiba and a dialysate meter manufactured by Precision Systems.
The results are shown in Table 3 below.

  As can be seen from the results in the table, the α-trino-ST water of the present invention showed stable pH and good osmotic pressure.

Example 4: Antibacterial test of dialysate containing electrolyte component / glucose using neutral electrolyzed water [Method]
In 1 L of α-trino-ST water (2 solutions of residual chlorine concentration: 3 ppm and 5 ppm), sodium chloride 6.25 g, potassium chloride 0.18 g, calcium chloride dihydrate 0.37 g, magnesium chloride hexahydrate A dialysate was prepared by dissolving 34 g, glucose 1.26 g, and sodium bicarbonate 2.52 g.
On the other hand, the same dialysate components were dissolved in distilled water as a control dialysate.
Each test solution was injected intraperitoneally into male rats weighing 200-232 g. The intraperitoneal injection was performed for 6 consecutive days, and the peritoneal fluid was collected on the 4th or 7th day, and the propagation of bacteria was observed with Sensimedia (registered trademark: made by Nipro).
In addition, the general state of rats was inferred from changes in body weight, and was substituted for clinical pathology.
On the 7th day, intraperitoneal injection is not performed and only intraperitoneal fluid is collected.

[result]
1. Observation of Bacterial Proliferation In the dialysate using distilled water as the control dialysate, colony formation was observed in the intraperitoneal fluid, and remarkable bacterial growth was observed.
On the other hand, in the dialysate using the α-trino-ST water of the present invention (residual chlorine concentration: 2 solutions of 3 ppm and 5 ppm), no colony formation showing bacterial growth was observed, which was good. It was observed that the antibacterial action was exhibited.

2. Influence on body weight Table 4 below shows changes in body weight.

As can be seen from the results shown in the table, there was a tendency for body weight to be decreased in rats that were intraperitoneally injected with dialysate using distilled water with bacterial infection. Death was confirmed in the case, and the cause of death was presumed to be worsening of the disease state and infection.
On the other hand, in rats injected intraperitoneally with a dialysate using α-trino-ST water of the present invention, it was estimated that the weight of the rats increased and the health of the rats was maintained. That is, by using the α-trino-ST water of the present invention, it is not necessary to contain citric acid, acetic acid, lactic acid, etc. in the preparation of the dialysate, and therefore side effects (hypotension, myocardial suppression, protein catabolism, anemia, Not only the appearance of bleeding tendency, hypocalcemia, etc.), but also the excellent bactericidal action prevents the occurrence of infectious diseases, which seems to have maintained the general condition of the rat well .

Judging from the above results, it was found that the dialysate using the neutral electrolyzed water of the present invention as a basic solution (dissolved solution) showed an excellent bactericidal effect due to residual chlorine, and the dialysis related circuit cleaning solution It was judged that it can be applied as well.
In addition, calcium chloride can be dissolved without producing insoluble calcium carbonate, and the pH of the dialysate is maintained neutral without relying on organic acids, and it is judged that an excellent dialysate can be provided. It was.

Example 5: Effect of inhibiting renal failure progression on rats with chronic renal failure using neutral electrolyzed water [Method]
(1) Experimental animals and their breeding For the experimental animals, 5-week-old male SD (Sprague-Dawley) rats (Claire Japan) with an average of 100 g were used. The feed (CE-2, Nippon Claire) and water were freely consumed and were bred in an air-conditioned animal room at a room temperature of 23 ° C. and a humidity of 55 ± 5% with a 12-hour light-dark cycle (light period 7-19 o'clock). The rats were subjected to 5/6 nephrectomy 2 weeks after the start of breeding, grouped 4 weeks later, and dissected after 4 weeks of intervention experiment.

(2) Preparation of 5/6 nephrectomized rat Under anesthesia of somnopentyl 0.5 mL / 100 g (manufactured by Kyoritsu Pharmaceutical Co., Ltd.), the abdomen was opened from the midline of the abdomen. The book was ligated with a 7-0 needled proline yarn (ETHICON: manufactured by J & J). Next, after ligating the entire right renal artery with 5-0 needle silk thread (ETHICON), the right kidney was completely removed, the abdominal muscle was silk thread with 5-0 needle (ETHICON), and the skin was bicyclyl with 4-0 needle. Sutured with thread (ETHICON).

(3) Experimental method 17 rats at 4 weeks after 5/6 nephrectomy were used as control group (n = 8), α-trino-ST water group of the present invention (residual chlorine concentration: 3 ppm solution) (n = 9) Divided into two groups.
Powdered feed (protein: 24.9 g / 100 g; energy: 346.8 kcal / 100 g, CE-2, Japan Claire) and drinking water were given tap water. After all the rats were maintained under the same breeding conditions for 4 weeks, the control group continued these conditions, and the α-trino-ST water group was changed from tap water to α-trino-ST water to start the intervention.
The α-trino-ST water used in this experiment is a treatment solution of 0.2% sodium chloride aqueous solution.
The intake of powdered feed and drinking water was free intake at any time. The groupings should be equalized for each group based on the urine protein, urine volume, systolic blood pressure, and the degree of renal failure at the time of 6/6 nephrectomy at 4 weeks after 5/6 nephrectomy. went.

(4) Measurement item 5/6 before nephrectomy is 0 W, 4 weeks after 5/6 nephrectomy is 4 W, 5 weeks after 5/6 nephrectomy is 8 W (4 weeks after the start of intervention), Body weight, systolic blood pressure measurement, blood collection, and 24-hour urine collection were performed at 0, 4, and 8 W, respectively.
The systolic blood pressure was measured by the tail cuff method without anesthesia, and the average value was obtained. Blood samples were collected from the femoral vein for 0 and 4W under ether anesthesia, and from the renal artery for 8W at the time of dissection. Hematocrit was measured using a part of the blood, and the rest was centrifuged, and only serum was collected. Stored at ° C. The 24-hour urine collection was performed using a metabolic gauge, the collected urine was centrifuged, and the supernatant was stored at -20 ° C.

(5) Renal glomerulosclerosis index At 8 weeks, the left residual kidney was removed, fixed in 4% PFA / PBS, embedded in paraffin, sliced 3 μm thick, and periodic acid shiff (PAS ) It dye | stained and observed with the 400 times optical microscope.
The degree of hardening of each glomerulus was evaluated based on the following five evaluation points, and the average of all glomeruli was calculated as SI.
0: No semi-quantitative curing 1: Curing degree of 25% or less 2: Curing degree of 26-50% 3: Curing degree of 51-75% 4: Curing degree More than 76%

[Results and discussion]
First, as shown in Tables 5 to 7 below, the time points divided into two groups of the control group and the α-trino-ST water group, that is, the fourth week of the experimental week, the body weight, blood pressure, urine volume, and creatinine clearance were the same. It has been confirmed in advance that these two groups have approximately the same level of chronic renal failure. The urea nitrogen value was slightly higher in the α-trino-ST water group.
Next, a comparative experiment of the control group of the chronic renal failure model and the α-trino-ST water group was performed under such conditions. As a result, as shown in the 8th experimental week of the table, the body weight showed a steady growth of 456.4 ± 23.0 g in the α-trino-ST water group, and the blood pressure was 148.5 ± 19.8 mmHg lower than that in the control group. Maintained, urine volume is high at 36.2 ± 8.2mL, urea nitrogen level is low at 49.40 ± 6.22mg / dL, creatinine clearance is high at 0.31 ± 0.21ml / min, and glomerulosclerosis index is 50-75% More than 76% of curing was kept low at 16.68 and 12.31.
That is, it was judged that renal failure rats in the α-trino-ST water group had mild renal impairment compared to rats not taking α-trino-ST.
In conclusion, it was speculated that α-trino-ST has the effect of reducing tissue damage or restoring function.

By the way, the total amount of chloride ions in the body is about 40 mEq / kg, of which about 75% is distributed in the extracellular fluid and the remaining about 25% is distributed in the intracellular fluid and bone tissue. That is, the extracellular fluid is kept within the range of 96 to 108 mEq. It is also a major anion of extracellular fluid along with carbonate ions.
The balance is maintained by Na metabolism and acid-base equilibrium. Nevertheless, the physiological role has not yet been elucidated.
Similar to the experimental data of streptozotocin (STZ) diabetic rats described as Example 6 described later, the results of this time were measured by direct current or pulse current while vibrating with a period of 10 to 200 Hz and an amplitude vibration of 0.01 to 15 mm. 1 to 5 ppm residual chlorine dissolved in neutral electrolyzed water obtained by electrolysis at a voltage of 1 to 30 V and a current density of 5 to 300 A / dm ² has the effect of breaking the conventional concept. It can be said that this suggests the possibility.

  Next, the actual clinical trial example using the α-trino-ST water of the present invention will be described and its effectiveness will be proved. Prior to clinical trials, sufficient informed consent has been given and consent has been obtained for clinical trials.

Clinical example:
Saline α-trino-ST water with 0.9% sodium chloride concentration for CAPD (continuous portable peritoneal dialysis) patients with peritoneal catheter outlet and tunnel infections. Summarize usage results.
All five cases were judged to be effective. Some of them are outlined below.

First example: Male (born in 1945)
CAPD was started in chronic kidney disease caused by multiple cystic kidneys.
Redness and pruritus around the exit area were observed, and an exit infection was diagnosed. Immediately, the outlet was sterilized with Sterihide disinfectant, and self-disinfection was performed at the same time.
Even after one month, the outlet infection did not show a tendency to heal, but rather, some granulation with purulent secretions was observed on the partially destroyed surface. For this reason, all the defective granulations were excised, applied with gentacin (antibiotic) ointment and covered with iodoform gauze. Every day from the 3rd day when these effects seem to disappear, the outlet was self-sterilized with a sterilide disinfectant at home every day.
One week later, redness at the site of infection at the exit site was reduced, but the defective granulation recurred, bleeding was easy, and purulent secretion was also observed.
I was given a visit one week later, but came three weeks later. The reason for this is that redness and pruritus disappeared completely after starting to use “Raw Food ST”, and he did not come to the hospital during this period. However, about 20 mL of “Raw Food ST” was placed in a syringe with a Teflon (registered trademark) blunt needle, and the outlet and the subcutaneous area around the catheter were self-cleaning. In fact, no bad granulation or redness was observed on the day, and the appearance of the healthy skin was almost determined.
Therefore, due to the situation of medical fee billing, we switched to the conventional self-disinfection of the outlet with Sterihide disinfectant.
After a month and a half, he visited regularly. During this time, there are times when redness and pruritus at the outlet of the peritoneal catheter may be felt, but at that time, it is said that it is self-cleaning with “Raw Eating ST”, and it is said that it will be relieved in about 12 hours after cleaning.

Second example: Male (born in 1944)
CAPD was introduced in chronic kidney disease due to nephrosclerosis.
The patient was hospitalized for 1 month with CAPD peritonitis. Streptococccuas vestibularis and salivarius were detected in the peritoneal drainage, but these were subsided with antibiotics.
The patient complained of pain over 5 cm in the subcutaneous catheter tunnel from the outlet of the peritoneal catheter to the second catheter cuff, and was diagnosed as an infection of the peritoneal catheter outlet and tunnel. From the outlet, drainage was observed, and fungi such as Candida albicans were detected as (++) strongly positive in the culture. Antibiotics such as minomycin were used.
Thereafter, Corynebacterium Sp (++) and Gram positive coccus (+) were detected in addition to Candida albicans from the culture of secretions from the peritoneal catheter outlet. The tenderness of the tunnel just above the second cuff was remarkable. Diflucan was also used. In addition to the conventional sterilide disinfection, cleaning disinfection with a carbon dioxide solution added with chlorine gas was also carried out, but there was no tendency to improve, and secretions were always observed from the outlet.
Eight months later, the peritoneal catheter outlet / tunnel infection recurred and complained of pain more extensively and extensively than the previous time in the subcutaneous catheter tunnel from the peritoneal catheter outlet to the second catheter cuff.
Staphylococcus lugdunosis (++) was produced from the culture of the secretion from the peritoneal catheter outlet. Crabit 200 mg (oral), rosefin 1 g (transvenous) was used for 5 days, and Candida albicans (++) was also observed. It was. Sterihydrate solution was used for cleaning and disinfecting the peritoneal catheter outlet, and intravenous infusion of 100 mg of diflucan was also started for mycosis.
Thereafter, the tenderness of the tunnel did not disappear even though there was a tendency to decrease, and antibiotics proceeded to use vancomycin 1 g. Intravenous infusion of 100 mg of diflucan was also continued.
However, since it was still detected by Candida albicans (++), the disinfectant was switched to “Saline ST”. In addition, a Teflon (registered trademark) blunt needle is inserted in the subcutaneous tunnel to the vicinity of the second cuff, and this solution is based on a physiological saline solution. Press-flushed.
The tenderness of the subcutaneous tunnel showed a tendency to alleviate and became localized just above the second cuff. Therefore, all antibiotics were discontinued and self-cleaned every day with 500 mL bottles containing “Raw Food ST” handed to the person. Sterihide, which had been used for daily self-cleaning until that time, was also canceled. At this point, CRP, which is an index of inflammation, slightly increased from 0.1 to 0.22.
Thereafter, no secretion from the exit was observed, and tenderness in the upper layer of the tunnel became more localized.
Washing with “Raw Food ST” has been discontinued and only disinfection with “Raw Food ST” at the exit has been achieved. CRP was further lowered to 0.08.

Third example: Female (born in 1945)
CAPD therapy was started in chronic kidney disease due to chronic glomerulonephritis.
Six months later, it has been introduced as a peritoneal catheter outlet infection. Staphylococcua epidermidis was observed in (++), and intravenous infusion of vancomycin 0.5 g and application of bactroban were started.
As a result, drainage from the peritoneal catheter outlet was not observed, but adhesion of serous secretions to the exchange gauze was still observed. Neisseria mucosa, Alcligenes xylosoxidase, and Staphylococcus carae were detected from the deposits. For this reason, washing with 100 mL of chlorhexidine and 100 mL of 0.05% stericlone W was started, and antibiotics were changed to 1 g of meropen and Bacter 2T.
Although the above treatment was continued, excretion of serous secretions remained unchanged. For this reason, the subcutaneous portion from the catheter outlet to the tunnel was washed with 100 mL of “Raw Food ST”. Antibiotic injection was discontinued, and oral chemotherapy was also discontinued.
As a result, the discharge of serous secretion from the catheter outlet was not observed, and the patient was transferred to the hospital.

  The above clinical examples show some clinical examples, but the use of “Raw Diet ST” for CAPD patients complicated with the exit part of the peritoneal catheter and the tunnel part infection includes other examples, All cases are judged to be effective.

The neutral electrolyzed water (α-trino-ST water) provided by the present invention has been confirmed to have various other excellent effects by animal experiments.
These points are listed for reference.

Example 6: Effect of α-trino ST water on suppression of blood glucose increase in streptozotocin (STZ) diabetic rats (1) Preparation of diabetes model animal
Iar: Long-Evans rats (weight: 180-200 g) streptozotocin (STZ) 65 mg / kg was administered intravenously once via the tail vein at a dose of 1 mL / kg body weight, and a diabetes model (n = 10) It was created.
(2) Method Powdered feed (protein: 24.9 g / 100 g; energy: 346.8 kcal / 100 g, CE-2, CLEA, Japan), drinking water was freely consumed until the end of the experiment.
The control group continued this until the end of the experiment, and the α-trino-ST water (treated water from 0.2% sodium chloride aqueous solution) group was changed to the α-trino-ST water from the 2nd week of the experimental model creation and changed to 4 Continued until eyes (experiment ended here).
Blood was collected from the tail vein 1 week and 2 weeks after administration, and blood glucose was measured. A glucocard and diasensor (manufactured by Sanofi-aventis) were used for blood glucose level measurement.

(3) Results and discussion Since hyperglycemia of 401.7 ± 54.2 mg / dL was confirmed in one week after STZ administration, it was divided into a control group (n = 5) and an α-trino-ST water group (n = 5).
The blood glucose levels after grouping were 348.5 ± 180.2 mg / dL in the control group and 385.4 ± 39.9 mg / dL in the α-trino-ST water group, showing little difference between the two groups, and slightly higher in the α-trino-ST water group. It was confirmed.
On the other hand, after the intervention experiment, the control group was 28.8 weeks later (4 weeks after the start of the experiment) 538.8 ± 81.35 mg / dL, the α-trino-ST water group was 405.2 ± 24.1 mg / dL, and the α-trino-ST water The blood glucose level of the group was significantly lower than that of the control group, and remained almost the same level as the second week at the start of the intervention.
From this, it was speculated that the α-trino-ST water of the present invention suppresses the progress of pancreatic damage caused by streptozotocin and further has a tissue restoring action.

As described above, the present invention provides an aqueous solution for dialysis using neutral electrolyzed water obtained by electrolyzing physiological saline with an electrolytic cell equipped with a low-frequency vibration stirrer. The excellent effects described below can be exhibited, and the medical contribution is great.
(1) A dialysis solution that is sterile and does not contain bacterial cell components such as bacteria, pathogenic microorganisms, and bacterial toxins can be provided to patients with end-stage chronic renal failure who cannot survive without dialysis therapy.
(2) A neutral dialysate that does not contain any substances that are inconvenient for the living body can be provided to patients with chronic renal failure.
(3) Since it is possible to provide a dialysis solution using neutral electrolyzed water prepared as a simple and inexpensive solution, it is possible to easily prepare a dialysis solution according to the demands of medical staff, and the residual chlorine It is possible to reduce the labor of medical staff because neutral electrolyzed water with different concentrations can be prepared by full automation.
(4) Since an antibacterial physiological saline can be provided, neutral electrolyzed water having a wide range of applicability can be provided.

Claims (8)

While oscillating physiological saline with a period of 10 to 200 Hz and an amplitude vibration of 0.01 to 15 mm, a direct current or a pulse current causes a voltage of 1 to 30 V and a current density of 5 to 300 A / dm ^2. An aqueous solution for dialysis comprising neutral electrolyzed water containing 1 to 500 ppm of residual chlorine obtained by electrolysis.   The aqueous solution for dialysis according to claim 1, which is used as a dialysis solution as hemodialysis therapy or a dialysis solution as peritoneal dialysis therapy.   The aqueous solution for dialysis according to claim 1, which is used as a dialysis solution for dissolving an electrolyte component, glucose and amino acids.   The aqueous solution for dialysis according to claim 3, wherein sodium hydrogen carbonate is used as an alkalizing agent.   The aqueous solution for dialysis according to claim 1, which is used for cleaning a dialysate-related circuit.   The aqueous solution for dialysis according to claim 1, which is used as a disinfectant for a peritoneal catheter or a catheter coupling part in peritoneal dialysis therapy.   The aqueous solution for dialysis according to claim 1, wherein the aqueous solution for dialysis is used as a disinfectant for intraperitoneal, subcutaneous and skin, and skin in peritoneal dialysis.   The aqueous solution for dialysis according to claim 6 or 7, wherein the aqueous solution is mixed with another physiological saline.